Program Director/Principal Investigator (Last, First, Middle): Lazzaro, Brian P. 1R01 AI083932-01 GENETIC NETWORK LINKING IMMUNITY TO ENERGETIC STRESS, METABOLISM, AND REPRODUCTION ABSTRACT Resistance to infection is determined by immune system activity and the overall physiological condition of the host. This project will determine how the seemingly disparate physiological processes of immunity, metabolism and reproduction are genetically linked to determine resistance to infection in the genetic model system Drosophila melanogaster. Although Drosophila is an insect, its immune and metabolic processes are sufficiently similar to those of vertebrates that it can serve as an informative model for human clinical biology. Drosophila is also an important model for other insects, including agricultural pests and disease vectors of public health relevance. The experiments described in this proposal will capitalize on the fact that Drosophila can be reared in large numbers under controlled conditions to determine how dietary nutrition interacts with genotype to shape immune-related and reproductive traits. Genetic and phenotypic correlations will be measured to establish pleiotropic control of immune-related, metabolic, and reproductive traits. Targeted genetic manipulation will be employed to determine genetic linkages among the measured traits and to infer how natural selection may operate simultaneously on these critical and physiologically intertwined traits, especially when they function in opposition to each other. REVISED PUBLIC HEALTH RELEVANCE STATEMENT SECTION Program Director/Principal Investigator (Last, First, Middle): Swain, Susan L. 1R01 AI076534-01A1 NO text